The Genotype-Tissue Expression (GTEx) project, a NIH Common Fund Initiative (http://nihroadmap.nih.gov/GTEx/), aims to provide a resource to the scientific community with which to study the relationship between genetic variation and regulation of gene expression. This project will collect and analyze multiple human tissues from donors who have been characterized for germline genetic variation through dense genotyping. By treating global RNA expression levels as quantitative traits, loci with polymorphisms that are highly correlated with variations in expression will be identified as expression quantitative trait loci, or eQTLs. The SNPs within the eQTL that are correlated with gene expression are sometimes called eSNPs. Based on analysis of individual tissues, approximately 4-12% of gene transcripts have cis-eQTLs, operationally defined as an eSNP that is located close to the gene whose expression it is correlated with. To identify trans-eQTLs, in which the eSNP maps far from the gene or on a different chromosome than the gene it is regulating, much larger sample sizes relative to cis-eQTLs, will be required. This is because of the need to adjust for the large number of statistical tests involved in searching for correlation between expression levels of every transcript and a very large number of genetic variants. Comprehensive identification of both cis- and trans-eQTLs will provide a valuable basis on which to study gene regulation, with an immediate application in interpreting genome-wide association studies findings.